Seminars

Relational thinking, or the process of identifying and integrating relations between mental representations, is regularly invoked during reasoning. This mental capacity enables us to draw higher-order abstractions and generalize across situations and contexts, and we have argued that it should be included in the pantheon of executive functions. In this talk, I will briefly review our lab's work characterizing the roles of lateral prefrontal and parietal regions in relational thinking. I will then discuss structural and functional predictors of individual differences and developmental changes in reasoning.

Neural systems are remarkably robust against various perturbations, a phenomenon that still requires a clear explanation. Here, we graphically illustrate how neural networks can become robust. We study spiking networks that generate low-dimensional representations, and we show that the neurons’ subthreshold voltages are confined to a convex region in a lower-dimensional voltage subspace, which we call a ‘bounding box.’ Any changes in network parameters (such as number of neurons, dimensionality of inputs, firing thresholds, synaptic weights, or transmission delays) can all be understood as deformations of this bounding box. Using these insights, we show that functionality is preserved as long as perturbations do not destroy the integrity of the bounding box. We suggest that the principles underlying robustness in these networks—low-dimensional representations, heterogeneity of tuning, and precise negative feedback—may be key to understanding the robustness of neural systems at the circuit level.

Gaining insight into the overlapping neural circuits that regulate positive and negative emotion is an important step towards understanding the heterogeneity in the aetiology of anxiety and depression and developing new treatment targets. Determining the core contributions of the functionally heterogenous prefrontal cortex to these circuits is especially illuminating given its marked dysregulation in affective disorders. This presentation will review a series of studies in a new world monkey, the common marmoset, employing pathway-specific chemogenetics, neuroimaging, neuropharmacology and behavioural and cardiovascular analysis to dissect out prefrontal involvement in the regulation of both positive and negative emotion. Highlights will include the profound shift of sensitivity away from reward and towards threat induced by localised activations within distinct regions of vmPFC, namely areas 25 and 14 as well as the opposing contributions of this region, compared to orbitofrontal and dorsolateral prefrontal cortex, in the overall responsivity to threat. Ongoing follow-up studies are identifying the distinct downstream pathways that mediate some of these effects as well as their differential sensitivity to rapidly acting anti-depressants.

Polaris Koi (Philosophy) and Jake Gavenas (Neuroscience) begin the seminar by arguing that agentive control is the key requirement for free will, drawing on folk-philosophy findings to support this claim (Gavenas et al., in prep). They explore how two executive control processes that functionally involve consciousness—inhibition and top-down control of attention—connect self-control and free will.

Dementia with Lewy bodies (DLB) is a synucleinopathy but more than half of patients with DLB also have varying degrees of tau and amyloid-β co-pathology. Identifying and tracking the pathologic heterogeneity of DLB with multi-modal biomarkers is critical for the design of clinical trials that target each pathology early in the disease at a time when prevention or delaying the transition to dementia is possible. Furthermore, longitudinal evaluation of multi-modal biomarkers contributes to our understanding of the type and extent of the pathologic progression and serves to characterize the temporal emergence of the associated phenotypic expression. This talk will focus on the utility of multi-modal imaging in DLB.

Dr. Looger will present updates on a variety of molecular tools for studying & manipulating neural circuits & other preparations. Topics include genetically encoded calcium indicators (including the new ultra-fast jGCaMP8 variants), neurotransmitter sensors (improved versions for following glutamate, GABA, acetylcholine, serotonin), optogenetic effectors including the new “enhanced Magnets” dimerizers, AAV serotypes for retrograde labeling & altered tropism, probes for correlative light-electron microscopy, chemical gene switches, etc. He will make all his slides freely available - so don’t worry about hurriedly taking notes; instead focus on questions and ideas for collaboration. Please bring your suggestions for molecular tools that would be transformative for the field.

The gradual accumulation of hyperphosphorylated forms of the Tau protein (pTau) in the human brain correlate with cognitive dysfunction and neurodegeneration. I will present our recent findings on the consequences of human pTau aggregation in the hippocampal formation of a mouse tauopathy model. We show that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to their neurodegeneration. In aged but not younger mice, pTau spreads to oligodendrocytes. During ‘goal-directed’ navigation, we detect fewer high-firing pyramidal cells, but coupling to network oscillations is maintained in the remaining cells. The firing patterns of individually recorded and labelled pyramidal and GABAergic neurons are similar in transgenic and non-transgenic mice, as are network oscillations, suggesting intact neuronal coordination. This is consistent with a lack of pTau in subcortical brain areas that provide rhythmic input to the cortex. Spatial memory tests reveal a reduction in short-term familiarity of spatial cues but unimpaired spatial working and reference memory. These results suggest that preserved subcortical network mechanisms compensate for the widespread pTau aggregation in the hippocampal formation. I will also briefly discuss ideas on the subcortical origins of spatial memory and the concept of the cortex as a monitoring device.

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. Over the past years, we used a combination we used a combination of extracellular recordings, neuronal decoding approaches, and state of the art optogenetic manipulations to identify key neuronal elements and mechanisms controlling defensive fear responses. I will present an overview of our recent work ranging from analyses of dedicated neuronal types and oscillatory and synchronization mechanisms to artificial intelligence approaches used to decode the activity or large population of neurons. Ultimately these analyses allowed the identification of high dimensional representations of defensive behavior unfolding within prefrontal networks.

In the Learning Salon, we will discuss the similarities and differences between biological and machine learning, including individuals with diverse perspectives and backgrounds, so we can all learn from one another.

Gravity is a constant in our lives. It provides an internalized reference to which all other perceptions are related. We can experimentally manipulate the relationship between physical gravity with other cues to the direction of “up” using virtual reality - with either HMDs or specially built tilting environments - to explore how gravity contributes to perceptual judgements. The effect of gravity can also be cancelled by running experiments on the International Space Station in low Earth orbit. Changing orientation relative to gravity - or even just perceived orientation – affects your perception of how far away things are (they appear closer when supine or prone). Cancelling gravity altogether has a similar effect. Changing orientation also affects how much visual motion is needed to perceive a particular travel distance (you need less when supine or prone). Adapting to zero gravity has the opposite effect (you need more). These results will be discussed in terms of their practical consequences and the multisensory processes involved, in particular the response to visual-vestibular conflict.

Existing studies show that there is a positive association between pro-migrant integration policies and the subjective well-being of immigrants. However, there is a lack of research elucidating the relations between migrant integration policies and the subjective well-being of the host (i.e., non-migrant) population. This study is based on European data and uses multilevel analysis to clarify the relations between migrant integration policy (both as a whole and its 8 separate components such as: Labour market mobility and Family reunion) and the subjective well-being of the non-immigrant population in European countries. We examined relations between the Migrant Integration Policy Index (MIPEX) for 22 countries in Europe and subjective well-being, as assessed by the European Social Survey (ESS) data. The results demonstrated that there is a positive relation between the MIPEX and subjective well-being for non-immigrants. Considering different components of the MIPEX separately, we found most of them being positively related to the subjective well-being of non-immigrants. As no negative relationship was identified between any of the eight MIPEX components and subjective well-being, policies in favour of immigrant integration also seem to benefit the non-immigrant population.